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转移性微环境中的异质性:JunB表达的微细胞作为黑色素瘤脑转移进展的潜在驱动因素

Orit Adir¹, Orit Sagi-Assif¹, Tsipi Meshel¹

¹The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Science, Tel Aviv University, Tel Aviv 6997801, Israel.

|October 28, 2023

概括

黑色素瘤大脑转移会触发各种微质反应,影响瘤的进展. 准具有高JunB表达的微质细胞可能为黑色素瘤大脑转移提供新的治疗策略.

科学领域:

神经瘤学神经瘤学
免疫学免疫学免疫学
癌症生物学癌症生物学

背景情况:

黑色素瘤大脑转移细胞 (MBM) 和微质细胞之间的相互信号改变了它们的表型.
微质表现出对MBM细胞的反应上调的转录因子JunB.

研究的目的:

调查微质JunB上调调节对MBM进展的影响.
了解JunB在微质细胞与黑色素瘤相互作用中的功能作用.

主要方法:

用于分子分析的RNA测序 (RNA-seq) 和逆相蛋白阵列 (RPPA).
产生过度表达 (JunBhi) 或下调 (JunBlo) 的微质细胞 JunB.
流细胞计和3D共同培养模型来评估微质功能和MBM细胞行为.

主要成果:

来自黑色素瘤细胞的白血病抑制因子 (LIF) 通过JAK/STAT3信号传递对微质JunB进行上调.
JunBhi微质细胞显示迁移和细胞酶的减少,并支持黑色素瘤细胞的增殖.
JunBlo微质细胞减少黑色素瘤的扩散和迁移.
在JunBhi和JunBlo细胞中观察到微质激活标记物 (Iba-1,CD150) 和免疫抑制分子 (SOCS3,PD-L1) 的差异表达.

结论:

黑色素瘤诱导异质的微质JunB表达,影响MBM的进展.
具有高JunB表达的微细胞支持MBM生长,而具有低JunB的微细胞则抑制它.
针对具有高JunB表达的微质,为MBM提供了潜在的治疗方法.

关键词:

JunB JunB JunB JunB JunB JunB JunB JunB JunB JunB JunB JunB JunB 大脑转移是大脑转移.免疫微观环境免疫微环境黑色素瘤是一种黑色素瘤.微质细胞中的微质细胞瘤微环境是一个微环境.

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